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Background: In treating malaria in Uganda, artemether-lumefantrine (AL) has been associated with a lower risk of recurrent parasitemia, compared with artesunate-amodiaquine (AS/AQ), but changing treatment practices may have altered parasite susceptibility.Methods: We enrolled 602 children aged 6-59 months with uncomplicated falciparum malaria from 3 health centers in 2013-2014 and randomly assigned them to receive treatment with AS/AQ or AL. Primary outcomes were risks of recurrent parasitemia within 28 days, with or without adjustment to distinguish recrudescence from new infection. Drug safety and tolerability and Plasmodium falciparum resistance-mediating polymorphisms were assessed.Results: Of enrolled patients, 594 (98.7%) completed the 28-day study. Risks of recurrent parasitemia were lower with AS/AQ at all 3 sites (overall, 28.6% vs 44.6%; P < .001). Recrudescences were uncommon, and all occurred after AL treatment (0% vs 2.5%; P = .006). Recovery of the hemoglobin level was greater with AS/AQ (1.73 vs 1.39 g/dL; P = .04). Both regimens were well tolerated; serious adverse events were uncommon (1.7% in the AS/AQ group and 1.0% in the AL group). AS/AQ selected for mutant pfcrt/pfmdr1 polymorphisms and AL for wild-type pfcrt/pfmdr1 polymorphisms associated with altered drug susceptibility.Conclusions: AS/AQ treatment was followed by fewer recurrences than AL treatment, contrasting with older data. Each regimen selected for polymorphisms associated with decreased treatment response. Research should consider multiple or rotating regimens to maintain treatment efficacies. [ABSTRACT FROM AUTHOR]

Background: A better understanding of case management practices is required to improve inpatient pediatric care in resource-limited settings. Here we utilize data from a unique health facility-based surveillance system at six Ugandan hospitals to evaluate the quality of pediatric case management and the factors associated with appropriate care. Methods: All children up to the age of 14 years admitted to six district or regional hospitals over 15 months were included in the study. Four case management categories were defined for analysis: suspected malaria, selected illnesses requiring antibiotics, suspected anemia, and diarrhea. The quality of case management for each category was determined by comparing recorded treatments with evidence-based best practices as defined in national guidelines. Associations between variables of interest and the receipt of appropriate case management were estimated using multivariable logistic regression. Results: A total of 30,351 admissions were screened for inclusion in the analysis. Ninety-two percent of children met criteria for suspected malaria and 81% received appropriate case management. Thirty-two percent of children had selected illnesses requiring antibiotics and 89% received appropriate antibiotics. Thirty percent of children met criteria for suspected anemia and 38% received appropriate case management. Twelve percent of children had diarrhea and 18% received appropriate case management. Multivariable logistic regression revealed large differences in the quality of care between health facilities. There was also a strong association between a positive malaria diagnostic test result and the odds of receiving appropriate case management for comorbid non-malarial illnesses - children with a positive malaria test were more likely to receive appropriate care for anemia and less likely for illnesses requiring antibiotics and diarrhea. Conclusions: Appropriate management of suspected anemia and diarrhea occurred infrequently. Pediatric quality improvement initiatives should target deficiencies in care unique to each health facility, and interventions should focus on the simultaneous management of multiple diagnoses. [ABSTRACT FROM AUTHOR]

Background: Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is widely recommended in sub-Saharan Africa to reduce the risk of malaria and improve birth outcomes. However, there are reports that the efficacy of IPTp with SP is waning, especially in parts of Africa where antimalarial resistance to this drug has become widespread. Methodology/Principal Findings: We conducted a cross-sectional study of 565 HIV-uninfected women giving birth at Tororo District Hospital in southeastern Uganda. The primary objective of the study was to measure associations between use of SP during pregnancy from antenatal records and the risk of adverse outcomes including placental malaria, low birth weight, maternal parasitemia and maternal anemia. The proportion of women who reported taking 0, 1, 2, and 3 doses of SP during pregnancy was 5.7%, 35.8%, 56.6% and 2.0% respectively. Overall, the prevalence of placental malaria was 17.5%, 28.1%, and 66.2% by placental smear, PCR, and histopathology, respectively. In multivariate analyses controlling for potential confounders, ≥2 doses of SP was associated with non-significant trends towards lower odds of placental malaria by placental smear (OR = 0.75, p = 0.25), placental malaria by PCR (OR = 0.93, p = 0.71), placental malaria by histopathology (OR = 0.75, p = 0.16), low birth weight (OR = 0.63, p = 0.11), maternal parasitemia (OR = 0.88, p = 0.60) and maternal anemia (OR = 0.88, p = 0.48). Using a composite outcome, ≥2doses of SP was associated with a significantly lower odds of placental malaria, low birth weight, maternal parasitemia, or maternal anemia (OR = 0.52, p = 0.01). Conclusions/Significance: In this area of Uganda with intense malaria transmission, the prevalence of placental malaria by histopathology was high even among women who reported taking at least 2 doses of SP during pregnancy. The reported use of ≥2 doses of SP was not associated with protection against individual birth and maternal outcome measures but did protect against a composite measure of any adverse outcome. [ABSTRACT FROM AUTHOR]

Background: Most African countries have adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. The World Health Organization now recommends limiting anti-malarial treatment to those with a positive malaria test result. Limited data exist on how these policies have affected ACT prescription practices. Methods: Data were collected from all outpatients presenting to six public health facilities in Uganda as part of a sentinel site malaria surveillance programme. Training in case management, encouragement of laboratory-based diagnosis of malaria, and regular feedback were provided. Data for this report include patients with laboratory confirmed malaria who were prescribed anti-malarial therapy over a two-year period. Patient visits were analysed in two groups: those considered ACT candidates (defined as uncomplicated malaria with no referral for admission in patients ⩾ 4 months of age and ⩾ 5 kg in weight) and those who may not have been ACT candidates. Associations between variables of interest and failure to prescribe ACT to patients who were ACT candidates were estimated using multivariable logistic regression. Results: A total of 51,355 patient visits were included in the analysis and 46,265 (90.1%) were classified as ACT candidates. In the ACT candidate group, 94.5% were correctly prescribed ACT. Artemether-lumefantrine made up 97.3% of ACT prescribed. There were significant differences across the sites in the proportion of patients for whom there was a failure to prescribe ACT, ranging from 3.0-9.3%. Young children and woman of childbearing age had higher odds of failure to receive an ACT prescription. Among patients who may not have been ACT candidates, the proportion prescribed quinine versus ACT differed based on if the patient had severe malaria or was referred for admission (93.4% vs 6.5%) or was below age or weight cutoffs for ACT (41.4% vs 57.2%). Conclusions: High rates of compliance with recommended ACT use can be achieved in resource-limited settings. The unique health facility-based malaria surveillance system operating at these clinical sites may provide a framework for improving appropriate ACT use at other sites in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: In 2011, Uganda's Ministry of Health switched policy from presumptive treatment of malaria to recommending parasitological diagnosis prior to treatment, resulting in an expansion of diagnostic services at all levels of public health facilities including hospitals. Despite this change, anti-malarial drugs are often prescribed even when test results are negative. Presented is data on anti-malarial prescription practices among hospitalized children who underwent diagnostic testing after adoption of new treatment guidelines., Methods: Anti-malarial prescription practices were collected as part of an inpatient malaria surveillance program generating high quality data among children admitted for any reason at government hospitals in six districts. A standardized medical record form was used to collect detailed patient information including presenting symptoms and signs, laboratory test results, admission and final diagnoses, treatments administered, and final outcome upon discharge., Results: Between July 2011 and December 2013, 58,095 children were admitted to the six hospitals (hospital range 3294-20,426).A total of 56,282 (96.9 %) patients were tested for malaria, of which 26,072 (46.3 %) tested positive (hospital range 5.9-57.3 %). Among those testing positive, only 84 (0.3 %) were first tested after admission and 295 of 30,389 (1.0 %) patients who tested negative at admission later tested positive. Of 30,210 children with only negative test results, 11,977 (39.6 %) were prescribed an anti-malarial (hospital range 14.5-53.6 %). The proportion of children with a negative test result who were prescribed an anti-malarial fluctuated over time and did not show a significant trend at any site with the exception of one hospital where a steady decline was observed. Among those with only negative test results, children 6-12 months of age (aOR 3.78; p < 0.001) and those greater than 12 months of age (aOR 4.89; p < 0.001) were more likely to be prescribed an anti-malarial compared to children less than 6 months of age. Children with findings suggestive of severe malaria were also more likely to be prescribed an anti-malarial after a negative test result (aOR 1.98; p < 0.001)., Conclusions: Despite high testing rates for malaria at all sites, prescription of anti-malarials to patients with negative test results remained high, with the exception of one site where a steady decline occurred.

The primary source of malaria surveillance data in Uganda is the Health Management Information System (HMIS), which does not require laboratory confirmation of reported malaria cases. To improve data quality, an enhanced inpatient malaria surveillance system (EIMSS) was implemented with emphasis on malaria testing of all children admitted in select hospitals. Data were compared between the HMIS and the EIMSS at four hospitals over a period of 12 months. After the implementation of the EIMSS, over 96% of admitted children under 5 years of age underwent laboratory testing for malaria. The HMIS significantly overreported the proportion of children under 5 years of age admitted with malaria (average absolute difference = 19%, range = 8-27% across the four hospitals) compared with the EIMSS. To improve the quality of the HMIS data for malaria surveillance, the National Malaria Control Program should, in addition to increasing malaria testing rates, focus on linking laboratory test results to reported malaria cases., (© The American Society of Tropical Medicine and Hygiene.)